Venom ex machina? Exploring the potential of cell-free protein production for biological discovery of venom
Abstract
Venoms are complex cocktails of potent biomolecules present in many animal lineages. They have been the subject of several biodiscovery programs in the past due to their potential applications in biomedical, agricultural, and industrial applications. Nevertheless, many venomous animals are relatively small and produce only small amounts of venom. Therefore, the most commonly used activity-guided biodiscovery pipeline cannot be effectively applied. Cell-free protein production could be an attractive tool for fast production of selected venom components without creating genetically modified organisms, promising rapid and highly efficient access to biomolecules for bioactivity studies. However, these methods have only been used sporadically in venom research, and their potential has yet to be established. Here, we investigate the ability of a prokaryote-based cell-free system to produce a range of venom toxins from different types and different source organisms. We show that only a limited number of toxins can be expressed in small amounts. Together with known problems in promoting correct folding, our preliminary investigations support that venom-tailored cell-free systems will likely need to be developed before this technology can be effectively used for venom biodiscovery.
